tbuckley/cabot-search huggingface dataset:
H22 Barking up the right tree: history of quinine
Authors: Alphonsus Yip, Sinthiya Sivarajah, Janakan Natkunarajah
Journal: British Journal of Dermatology (2023)

Abstract Quinine is considered to be one of the most important medical discoveries of the 17th century through its use in treating malaria. Since then, its applications have expanded, and quinine continues to be one of the most widely used drugs in dermatology. Quinine is found in the bark of the Cinchona tree found in the jungles of the Andean region of South America. The exact nature of its discovery remains unclear; however, there are tales of the Spanish Countess of Chinchon being cured of a recurring fever by using liquid containing Cinchona bark. This prompted her to return to Spain in 1638 with the seeds and precious bark; in 1742, botanist Carl Linnaeus named the tree Cinchona in her honour. During the early 17th century, the bark was ground into a powder and mixed with wine. In 1820, French scientists Pierre Pelletier and Joseph Caventou developed the processes to extract quinine from Cinchona bark, improving the potency of the medicine. In the 19th century, as the role of quinine in treating malaria spread, Europeans in the British colonies started planting Cinchona trees to avoid importing large amounts of the drug. Owing to its bitter taste, quinine was mixed with sugar and soda, creating the first tonic water. The tonic water was mixed with gin to make the bitterness of quinine more palatable. Winston Churchill claimed that this drink ‘saved more Englishmen’s lives, and minds, than all the doctors in the Empire’ (Simonetti O, Contini C, Martini M. The history of Gin and Tonic; the infectious disease specialist long drink. When gin and tonic was not ordered but prescribed. Infez Med 2022; 30:619–26). The first documented use of quinine to treat dermatological conditions was produced by Payne in 1894, who reported the successful treatment of skin lesions in discoid lupus erythematosus (Payne J. A postgraduate lecture on lupus erythematosus Clin J 1894; 4:223–9). In 1951, a case series in the Lancet of 20 patients with lupus erythematosus and rheumatoid arthritis who were successfully treated with quinacrine, led to the extensive use of antimalarials to treat skin and joint conditions (Page F. Treatment of lupus erythematosus with mepacrine. Lancet 1951; 258:755–8). This was later succeeded by chloroquine: a synthetic analogue was first synthesized in the 1930s by Hans Andersag. However, it was noted to have significant toxicities, which led to the production of hydroxychloroquine, a similar drug with a much-improved side-effect profile. After 400 years, quinine and its synthetic derivatives continue to play a major role in managing dermatological conditions.
P94 Bimekizumab early treatment response translated into cumulative benefits in health-related quality of life in patients with moderate-to-severe plaque psoriasis: results from 2 years of the BE RADIANT phase IIIb trial
Authors: Philip Hampton, Patrick Brunner, Kamran Ghoreschi, Wolf-Henning Boehncke, Rhys Warham, Valerie Ciaravino, Balint Szilagyi, Fabienne Staelens, Amy Foulkes
Journal: British Journal of Dermatology (2023)

Abstract Speed of response is a key treatment goal for patients with psoriasis. This analysis aimed to assess how early clinical response translated into cumulative health-related quality of life (HRQoL) benefit in patients with moderate-to-severe plaque psoriasis over 2 years of bimekizumab (BKZ) treatment. Included patients from BE RADIANT were randomized to BKZ 320 mg every 4 weeks (Q4W), continued to receive Q4W dosing or switched to Q8W at week 16 and entered the open-label extension (OLE) at week 48 (receiving BKZ Q4W or Q8W; NCT03536884). The proportions of patients achieving Psoriasis Symptoms and Impacts Measure (P-SIM) 0 in itching, skin pain and scaling, and Dermatology Life Quality Index 0 or 1 (DLQI 0/1), were estimated using modified nonresponder imputation (mNRI); missing data were imputed via NRI for patients discontinuing due to the lack of efficacy or treatment-related adverse events and multiple imputation otherwise. Cumulative HRQoL and symptom benefit through to week 96 was estimated using the area under the curve (AUC0–96) by week 16 Psoriasis Area and Severity Index (PASI)-100 status (NRI), with week 16 and week 96 responses also reported. AUC0–96 was used to calculate the estimated number of days that each response was achieved. Of the 336 patients randomized to BKZ who entered the OLE, 216 achieved PASI 100 at week 16. Of these, 187/216 patients had already achieved PASI 100 at one or more visit(s) before week 16. Of the PASI-100 responders at week 16, 71.8%, 92.1%, 89.4% and 88.0% also achieved P-SIM 0 for itching, skin pain and scaling and DLQI 0/1, respectively, vs. 39.1%, 77.7%, 56.6% and 74.6% of nonresponders. Of the week 16 PASI-100 responders at week 96, 67.1%, 85.4%, 80.6% and 89.3% achieved P-SIM 0 for itching, skin pain and scaling and DLQI 0/1, respectively, vs. 55.6%, 77.7%, 63.7% and 80.8% of nonresponders. The total AUC0–96 for achievement of P-SIM 0 in itching, skin pain and scaling and DLQI 0/1 was greater for week 16 PASI-100 responders through 2 years, corresponding to a greater number of days achieving these outcomes vs. nonresponders (Table 1). A high proportion of patients achieved complete skin clearance at week 16, translating to a greater number of days achieving P-SIM 0 in itching, skin pain and scaling and DLQI 0/1 vs. week 16 PASI-100 nonresponders through 2 years of BKZ treatment.Table 1AUC0-96 by week 16 PASI-100 response over 2 years (mNRI)Week 16 PASI-100 responders (n = 216)Week 16 PASI-100 nonresponders (n = 120)P-SIM 0P-SIM 0ItchingSkin painScalingDLQI 0/1ItchingSkin painScalingDLQI 0/1AUC0–9666398504784982674918753957837584Days465595549579344528405531 Acknowledgment: Medical writing: Costello Medical. Funding sources: UCB Pharma.
P19 Diagnostic conundrums in paraneoplastic pemphigus
Authors: Sarah Fleming, Jane Setterfield, John Mee, Helen Barrett, Karen Eustace
Journal: British Journal of Dermatology (2023)

Abstract Paraneoplastic pemphigus (PNP) is a subset of pemphigus, a group of autoimmune blistering skin disorders. A 51-year-old man presented with paraneoplastic pemphigus associated with a hepatic neoplasm. He described an epigastric mass and associated mucositis affecting the orogenital mucosae, as well as the sclerae. Both computed tomography and magnetic resonance imaging demonstrated a 14-cm mass arising from the left lobe of the liver. A liver biopsy showed features of an atypical spindle-cell neoplasm, but a definite diagnosis was not possible. A diagnostic skin biopsy was taken from his outer lip mucosae. Histology showed surface ulceration with an acute inflammatory infiltrate, lichenoid lymphoplasmacytic infiltrate with focal basal vacuolar change, degenerate keratinocytes and adjacent suprabasal acantholysis and spongiosis. Perilesional direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) showed intercellular IgG antibodies on transitional epithelium with a high titre of 1 : 800 to rat bladder. These finding were consistent with the suspected clinical diagnosis of paraneoplastic pemphigus. The patient was commenced on oral prednisolone 1 mg kg−1 daily. Topical therapy included budesonide mixed with sweetener applied to the oral mucosae. Following this, a trial of 3 days of intravenous methylprednisolone along with 2% cocaine mouthwash, triple mouthwash (betamethasone, doxycycline and nystatin) and Dermovate® ointment was commenced, with improvement noted in pain, haemorrhage and ulceration. Intravenous immunoglobulin was administered preoperatively. The patient was subsequently transferred to a specialist centre for hepatobiliary surgery and listed for debulking of the liver mass. Postoperatively, he had plasmapheresis, with a noted reduction in mucosal ulceration and significant improvement in pain. Chemotherapy with doxorubicin and ifosfamide was initiated thereafter. PNP is a severe autoimmune blistering disorder characterized clinically by flaccid blisters and erosions. Although much is yet to be understood regarding the pathophysiology of PNP, studies show that the development of autoantibodies to the plakin family and desmogleins 1 and 3 play a particular role in its pathogenesis. In addition to autoantibodies, CD8+ T cells have also been shown to contribute to the development of PNP. In adults, the majority of cases are associated with an underlying haematological malignancy and, rarely, a solid-organ tumour. DIF findings include IgG and C3 deposition along the intercellular and basement membrane zones, while IIF detects autoantibodies to proteins found in transitional or stratified squamous epithelium. As in our case, reports have shown that the DIF can be negative, with one study showing a positive DIF in only 41% of cases. This case highlights the complex diagnostic and treatment challenges practitioners face when dealing with PNP and the patients it affects.
DP21 Thymoma and the skin: manifestations of multiorgan autoimmunity
Authors: Beth Peterknecht, Helen Lewis, Eanas Bader, Georgina Fremlin
Journal: British Journal of Dermatology (2023)

Abstract We present three patients who developed distinct cutaneous manifestations of thymoma: a rare mediastinal tumour. A 25-year-old man was treated for myasthenic crisis. Past medical history included thymectomy in 2016. Admission imaging confirmed recurrence of thymoma. He developed a red–brown macular rash affecting the trunk, back and thighs. Biopsy showed a florid lichenoid dermatitis consistent with graft-versus-host disease (GVHD). After resolution with steroids and mycophenolate mofetil, he subsequently developed a Stevens–Johnson syndrome/toxic epidermal necrolysis-like eruption with erythroderma and epidermal loss. Unfortunately, he developed multiorgan failure and died shortly afterward. A 43-year-old man presented to the emergency dermatology clinic with a 4-month history of a blistering rash affecting the chest and limbs. His previous medical history was significant for thymoma in 2008 and a recurrence in 2013. Skin biopsy demonstrated changes suggestive of bullous pemphigoid, and repeat computed tomography confirmed the recurrence of thymoma. Enzyme-linked immunosorbent assay testing was positive for bullous pemphigoid 180. He has responded well to prednisolone and doxycycline. A 51-year-old woman was reviewed in 2020 and 2021 with pruritic hyperpigmented patches affecting the face, trunk and limbs. Her past medical history included several relapses of thymoma with occurrence in 2002 and relapses in 2007, 2008, 2011, 2015 and 2021. Skin biopsy in June 2021 showed features of cutaneous GVHD. She received ruxolitinib and tapering steroids for thymoma-associated multiorgan autoimmunity (TAMA)-like GVHD and has had a remarkable improvement in her skin disease. Thymoma is described as a rare neoplasm, and up to 34% of thymomas are thought to be accompanied by symptoms of autoimmunity. The most frequently described syndromes include myasthenia gravis, pure red blood cell aplasia and hypogammaglobulinaemia. Other reported presentations include panencephalitis, enterocolitis and autoimmune hepatitis. Thymoma and cutaneous autoimmune presentations have been previously described, often in association with two rare syndromes: TAMA and paraneoplastic autoimmune multiorgan syndrome (PAMS). Both conditions demonstrate variability in clinical phenotype, driven by the activation of humoral and cellular immune responses. Clinically, patients may present with a spectrum of skin disease, including GVHD-like exanthems, lichen planus-like disease and pemphigus-like and pemphigoid-like lesions. Our case series demonstrates the heterogeneous cutaneous manifestations of thymoma-induced autoimmunity. We also describe two extremely rare phenomena accompanying thymomas: TAMA and PAMS. We also suggest that there is much crossover between these syndromes and previous definitions may require further review. This case series also highlights the importance of the wider multidisciplinary team in managing these patients and the complexities of their disease.
BT12 A comparison of outcomes and cost-effectiveness in a teledermatology vs. a standard face-to-face 2-week wait UK model
Authors: Fiza Ahmed, Richard Barlow, Sarah Mehrtens, Ravinder Atkar, Montserrat Gilaberte, Arucha Ekeowa-Anderson, Andrew Maguire, Zeeshaan Hasan, Padma Mohandas
Journal: British Journal of Dermatology (2023)

Abstract Teledermatology (TD) assessment of lesions referred on the 2-week wait (2WW) pathway reduces the need for in-person review, and thus facilitates increased clinical capacity. Although studies have demonstrated that TD can be cost-effective compared with a standard face-to-face (F2F) model, there is a lack of literature on the cost-effectiveness of TD with medical photography in the UK 2WW skin cancer pathway (Snoswell C, Finnane A, Janda M et al. Cost-effectiveness of store-and-forward teledermatology. JAMA Dermatol 2016; 152:702). In this study, we undertook a retrospective analysis of a store-and-forward TD 2WW pathway supported by medical photography at a UK centre (October–November 2022). As a comparator, we looked at the outcomes of a 2WW F2F clinic that took place 1 year earlier. Primary outcomes included comparing costs associated with both TD and F2F clinics, and outcomes after initial TD vs. F2F review (discharges, surgeries and subsequent F2F reviews). Inclusion criteria for TD were age 18–60 years, &amp;lt; 3 lesions referred and lesions being on culturally nonsensitive body sites. Cost estimates were included for physicians, nurses, healthcare assistants, administration staff and medical photographers. The tariff per 2WW skin cancer referral to the trust is £159.27. In total, 292 patient images were reviewed virtually in this study. Thirty of 68 patients in the F2F group met the same age criteria as those in the TD group (18–60 years), and thus these patients were used as comparators. Each 4-h TD session comprised an assessment of 25 patients vs. 12 patients per F2F session. Discharge rates from the first clinic appointment were higher for F2F clinics than for TD clinics (76.7% vs. 58.6%). Referrals for surgery were similar between the two groups (16.7% for F2F and 17.8% for TD). However, we found there were substantially more follow-ups requested after TD assessment vs. patients reviewed in F2F clinics (23.2% vs. 6.7%). The nonattendance rate for TD was 36 of 328 patients (11.0%) vs. five of 73 (6.8%) for F2F. Per-patient cost of the TD pathway was estimated to be £16.16 vs. £25.68 for a F2F 2WW appointment. Total revenue to the trust per clinical session was estimated to be £3981.75 (TD) vs. £1911.24 (F2F). This represented additional revenue of approximately £1975 for TD. Twenty-nine of 33 TD patients who completed feedback questionnaires reported overall satisfaction with the TD pathway. In this study, outcome rates between TD and F2F groups were similar in terms of planned surgeries. Planned subsequent F2F review rates were higher for TD, and discharge rates were higher for F2F. The revenue to the trust was greater for TD than F2F.
010 Enhanced outcome prediction in cutaneous squamous cell carcinoma using deep-learning and computational histopathology (cSCCnet)
Authors: Emilia Peleva, Yue Chen, Hasan Rizvi, Catherine Harwood, Jun Wang
Journal: British Journal of Dermatology (2023)

Abstract Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer and leads to a significant disease burden. Although metastases occur in &amp;lt; 5% of patients, effective treatments are limited and 5-year survival is poor, with mortality rates equivalent to those of melanoma in some regions of the world. Despite recent advances in understanding the molecular pathogenesis of cSCC, patient risk stratification is limited and based on clinicopathological staging, with few validated prognostic biomarkers available to guide management [de Jong E, Lammerts MUPA, Genders RE, Bowes Bavinck JN. Update of advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2022; 36(Suppl. 1):6–10]. In this study, we aimed to use artificial intelligence technology to develop a deep learning model using digitized whole-slide images of cSCC to quantify the risk of metastasis. Routine haematoxylin and eosin-stained slides of 256 primary cSCCs from immunocompetent patients at four collaborating centres were scanned. The area of interest encompassing tumour and peritumoral stroma was annotated, and 512 × 512 pixel tiles were generated from each slide. High-quality tiles (containing sufficient tumour content) were pooled together, with patient-level labels inherited by tiles. We trained multiple models using an 80:10:10 split for training, validation and testing, and the model achieving the highest tile- and slide-level validation accuracy was identified (ResNet50). The final model, namely, cSCCnet, achieved 88% sensitivity, 73% specificity, 64% positive predictive value and 92% negative predictive values on the independent test set. Blinded review of the top predictive tiles by three histopathologists suggested that the predictive features identified by cSCCnet were distinct from histopathological features commonly used by clinicians to estimate metastatic risk. We have demonstrated that it is possible to train a deep learning model using digital pathology to predict the risk of metastasis. cSCCnet surpassed the published performance of currently used staging systems, as well as commercially available gene panel testing (de Jong et al.; Wysong A, Newman JG, Covington KR et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol 2021; 84:361–9). The morphological features and patterns identified by cSCCnet are different from established histopathological high-risk criteria, indicating that this technology can enhance current practice. Although further validation in a prospective cohort is pending, this is an important step toward creating a risk stratification tool that can be incorporated into routine pathology workflows, significantly improving patient outcomes for this common cancer.
P20 A mysterious case of recurrent malignant melanoma
Authors: Meghana Mandala, Noor Awash
Journal: British Journal of Dermatology (2023)

Abstract A 74-year-old White man presented to community dermatology services in 2020 with one lesion on the right temple and one on the left forehead. These were investigated with punch biopsies and reported as benign intradermal melanocytic naevi. One year later, he was referred to our teledermatology clinic with a pink nodule on the right temple, which had never healed following the 2020 biopsy. The teledermatology photos were more in keeping with basal cell carcinoma (BCC) and he was booked in for an excision. Histology reported the lesion as ulcerated invasive malignant melanoma (Breslow thickness 3.1 mm and mitotic figures). At this stage, previous biopsies from 2020 were reviewed and invasive malignant melanoma (MM) was confirmed. He was reviewed in the clinic and, on skin examination, he had a 7-mm BCC on the right upper nasal bridge. We found a small scar, but no lesions, on the left temple. He had areas of psoriasis on his elbows and knees. No organomegaly or lymphadenopathy was identified on systemic examination. He underwent wide local excision (WLE) of the right temple MM scar with sentinel lymph node biopsies from the right neck, which were negative. Initial radiological imaging did not show any metastases. Three-month follow-up computed tomography showed colon thickening, and the patient was diagnosed with hepatic flexure tumour, which was treated with right hemicolectomy. Further imaging showed no evidence of metastases. In September 2022, a new 6-mm, light-brown indentation was identified on the medial edge of the melanoma scar on the right temple. Initially, the biopsy results reported recurrent melanoma. Further histological slide review and immunochemical analysis demonstrated langerin with multinucleated histiocyte-like cell infiltrates and lymphohistiocytic inflammatory cell infiltrates; Langerhans cell histiocytosis (LCH) was diagnosed. He underwent WLE of this lesion and positron emission tomography; we are still awaiting the results. He has been referred to a specialist haematology team and is awaiting further management. LCH is a rare, multisystem haematological disorder of the clonal proliferation of Langerhans cells. Existing case reports document LCH with concomitant presentations of myeloproliferative disorders, particularly myeloid leukaemias, or noncutaneous manifestations, including pulmonary presentations. To the best of our knowledge, there have been no reports of LCH presenting exclusively with cutaneous manifestations clinically mimicking recurrent MM. The rare incidence and misleading presentation of LCH often results in its lack of consideration as a differential diagnosis for recurrent solitary skin lesions in adults. This case also highlights the diagnostic challenges and thorough investigation required for this unique condition.
BT02 Use of teledermatology in the 2-week wait pathway: 5 years of positive data
Authors: Jennifer Elias, Hannah Synan-Jones, Rakhi Singh-Raghunath, Christina Vlachou, Bernadette De Silva
Journal: British Journal of Dermatology (2023)

Abstract Our teledermatology service was started in 2018 to facilitate the dermatology department’s move offsite and allow for the continuation of inpatient care digitally without the need for increasing staff levels or cross-site working. Its implementation also allowed for efficient adaptation and use throughout the COVID-19 pandemic and recovery following this period. Alongside these aspects, teledermatology has become integral in the department’s rapid-access 2-week wait (2WW) capacity. The pathway involves patients attending the department and undergoing a nurse-led review with upload of the history alongside macroscopic and dermoscopic photographs to the platform for consultant review and management. The platform conforms to all aspects of the British Association of Dermatologists’ teledermatology guidelines and is hosted on the National Health Service’s Health and Social Care Network. Of almost 4000 2WW referrals assessed by digital teledermatology between 2018 and the present, no referrals have been rejected for poor quality, only 1% required urgent face-to-face review with a consultant, 32% were discharged, 53% were booked in for a minor surgical procedure of which half were suspected to be cancer or precancer and performed urgently, and 14% were booked for routine review due to risk factors such a multiple moles and need for a full skin check. Our consultants can assess 40 patients on the digital platform in a 4-h period, and the overall cost is approximately half of a face-to-face clinic, including admin. Of all 2WW referrals, general practitioner diagnosis has remained quite constant, with 30% of lesions thought to be malignant melanoma (MM), 36% squamous cell carcinoma (SCC) and 3% basal cell carcinoma (BCC); in the remaining 31%, no diagnosis was made. Of those referred for surgery by the dermatology consultants, the clinical diagnosis was BCC in 20%, SCC in 22% and MM or MM in situ in 6%; the remainder was thought to be precancerous, atypical naevi or other. We have continued to demonstrate through audit that the clinicopathological correlation in the digital teledermatology clinic is as good as face-to-face clinics for lesion diagnosis because of the quality of the history and images. Our most recent satisfaction survey in 2022 showed 96% patient satisfaction with the initial teledermatology assessment; of those booked for a procedure, 88% strongly agreed that all concerns were addressed prior to surgery. All patients would recommend the service to friends and family. With nearly 5 years of data and continuous evaluation, we have shown the effectiveness of a well-designed, connected digital system in supporting our service without duplication of effort by clinicians or prolongation of the patient’s journey.